Liver diseases are among the 10 leading causes of death in the United States. The liver's extraordinary regenerative capacity is critical to understanding the mechanisms leading to developmental defects, acute and chronic liver diseases, and liver carcinogenesis. Stimulation of hepatocyte proliferation while preventing apoptosis is essential to the liver's regenerative process. Recently we uncovered a tumor suppressor pathway has potent effects upon liver cell division and death. Our long range goal is to define the cellular mechanisms underlying liver regeneration in health and disease and to apply these findings to developing improved therapies for liver disease. To that end, we are uniquely capable to address the objectives of this application, which are to uncover the mechanism that leads to the novel tumor suppressors' profound effects upon the liver. The central hypothesis of this proposal is that: The tumor suppressor controls liver celgrowth factor pathway in controlling liver size. At the end of the study we will better understand the growth and death of liver cells. This will help develop treatment for many liver diseases such as liver transplantation, cirrhosis, acute and chronic hepatitis. Project Narrative: The objectives of this study are to uncover a newly recognized very potent molecular system that controls the growth and death of the liver cells. Unlocking how this pathway works will help develop treatment for many liver diseases such as liver transplantation, cirrhosis, acute and chronic hepatitis.